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Related Experiment Videos

Two distinct pathways of positive selection for thymocytes

K Akashi1, M Kondo, I L Weissman

  • 1Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. Akashi@Darwin.Stanford.edu

Proceedings of the National Academy of Sciences of the United States of America
|April 16, 1998
PubMed
Summary

Two pathways, c-Kit+ and c-Kit-, guide thymocyte positive selection. Signals via c-Kit and interleukin-7 receptor (IL-7R) support these crucial T cell development steps.

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Area of Science:

  • Immunology
  • Developmental Biology
  • Cell Biology

Background:

  • T cell development involves positive selection to ensure T cells recognize self-MHC.
  • Two main pathways, c-Kit+ and c-Kit-, are involved in thymocyte positive selection.
  • The roles of c-Kit and IL-7R signaling in these pathways are not fully elucidated.

Purpose of the Study:

  • To investigate the distinct roles of c-Kit and IL-7R signaling in thymocyte positive selection pathways.
  • To elucidate the transition dynamics between c-Kit+ and c-Kit- pathways during T cell development.
  • To understand how thymocytes failing selection on one pathway are processed.

Main Methods:

  • Flow cytometry analysis of thymocyte subpopulations.
  • Tracking of T cell receptor (TCR) expression levels.

Related Experiment Videos

  • Analysis of cell surface markers including c-Kit and IL-7R.
  • Investigation of cell division and lineage commitment.

    • Main Results:

    • c-Kit and IL-7R signals mediate positive selection during the transition from TCRalpha/betaloCD4(int)/CD8(int) (DPint) c-Kit+ cells to transitional intermediate cells.
    • Thymocytes failing positive selection on the c-Kit+ pathway become TCRalpha/betaloc-Kit- (DPhi) blasts, potentially undergoing alternative TCRalpha rearrangements.
    • Rare DPhi c-Kit- blast cells up-regulate IL-7R (but not c-Kit) and serve as progenitors for the c-Kit-IL-7R+ pathway, which is CD4 lineage committed.
    • Cell division is characteristic of the TCRlo-medc-Kit+ transition but not essential for CD4 lineage maturation from DPhi c-Kit- blasts.

    Conclusions:

    • Positive selection in thymocytes occurs via distinct c-Kit+ and c-Kit- pathways.
    • The c-Kit- pathway functions as a salvage mechanism for cells that failed positive selection on the c-Kit+ pathway.
    • IL-7R signaling is critical for the c-Kit- pathway and CD4 lineage commitment, particularly in cells that have undergone TCRalpha rearrangement salvage.